The ultimate objective of this program is to determine if there may be detrimental health effects with human marihuana use because of retention of cannabinoids. In previous in vivo studies, we observed a long-retained metabolite in the livers, spleens, and fat of rats 15 days after a single I.V. or chronic I.P. injection of C14-delta 8-THC or C14-delta 9-THC. Because of the low concentration of the metabolites to lipid contamination in the tissue we were unable to satisfactorily isolate and purify either of these cannabinoids for MS, IR, or NMR analyses. We have since developed an in vitro liver microsomal system for producing these unknown metabolites in which a tenfold greater concentration of the parent compound (11-hydroxy-delta 8-THC or 11-hydroxy-delta 9-THC) can be used. One of the objectives of this project is to produce the unidentified retained metabolite of delta 9-THC with the in vitro system so that it will be of sufficient quantity for ultimate purification and analyses by GC/MS, IR, and NMR. The other objective of this project is to study the effect of this delta 9-THC retained metabolite on the liver drug metabolizing microsomal enzyme system.